Lot-to-lot verification is an integral component for monitoring the long-term stability of a measurement procedure. The practice is challenged by the resource requirements as well as uncertainty surrounding experimental design and statistical analysis that is optimal for individual laboratories, although guidance is becoming increasingly available. Collaborative verification efforts as well as application of patient-based monitoring are likely to further improve identification of any differences in performance in a relatively timely manner. Appropriate follow up actions of failed lot-to-lot verification is required and must balance potential disruptions to clinical services provided by the laboratory. Manufacturers need to increase transparency surrounding release criteria and work closer with laboratory professionals to ensure acceptable reagent lots are released to end users. A tripartite collaboration between regulatory bodies, manufacturers, and laboratory medicine professional bodies is key to developing a balanced system where regulatory, manufacturing, and clinical requirements of laboratory testing are met, to minimize differences between reagent lots and ensure patient safety. Clinical Chemistry and Laboratory Medicine has served as a fertile platform for advancing the discussion and practice of lot-to-lot verification in the past 60 years and will continue to be an advocate of this important topic for many more years to come.